TY - JOUR
T1 - Maternal obesity alters endoplasmic reticulum homeostasis in offspring pancreas
AU - Soeda, Jumpei
AU - Mouralidarane, Angelina
AU - Cordero, Paul
AU - Li, Jiawei
AU - Nguyen, Vi
AU - Carter, Rebeca
AU - Kapur, Sabrina R.
AU - Pombo, Joaquim
AU - Poston, Lucilla
AU - Taylor, Paul
AU - Vinciguerra, Manlio
AU - Oben, Jude A.
PY - 2016/3/15
Y1 - 2016/3/15
N2 - The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p <0.001) and plasma leptin (p <0.001) and decreased insulin (p <0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p <0.1 to p <0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults.
AB - The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p <0.001) and plasma leptin (p <0.001) and decreased insulin (p <0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p <0.1 to p <0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults.
KW - Autophagy
KW - ER stress
KW - Fatty pancreas
KW - Obesity
KW - Perinatal programming
KW - UPR
UR - http://www.scopus.com/inward/record.url?scp=84961141619&partnerID=8YFLogxK
U2 - 10.1007/s13105-016-0476-6
DO - 10.1007/s13105-016-0476-6
M3 - Article
AN - SCOPUS:84961141619
SN - 1138-7548
SP - 1
EP - 11
JO - JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
JF - JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
ER -
